Knockout of nephron ATP6AP2 impairs proximal tubule function and prevents high fat diet induced obesity in male mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Silas A Culver ◽  
Safia Akhtar ◽  
Callie Rountree-Jablin ◽  
Susanna R Keller ◽  
Helen P Cathro ◽  
...  
Keyword(s):  
Body Weight ◽  
Proximal Tubule ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Caloric Intake ◽  
Normal Diet ◽  
Male Mice ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Urinary Glucose

Abstract ATP6AP2 expression is increased in the nephron during high fat diet (HFD) and its knockout (ATP6AP2 KO) reduces body weight (WT) in mice. We evaluated the contribution of ATP6AP2 to urinary glucose (UG) and albumin (Ualb) handling during HFD. We hypothesized that nephron ATP6AP2 KO increases UG and Ualb and minimizes HFD-induced obesity. Eight-week old male C57BL/6J mice with inducible nephron specific ATP6AP2 KO and non-induced controls (C) were fed either normal diet (ND, 12% kcal fat) or HFD (45% kcal fat) for 6 months. ATP6AP2 KO mice on ND had 20% (p<0.01) lower WT compared to C. HFD fed mice had 41% (p<0.05) greater WT than ND fed C. In contrast, ATP6AP2 KO abrogated the increase in WT induced by HFD by 40% (p<0.05). Mice on HFD had less caloric intake compared to ND controls (p<0.01). There were no significant differences in metabolic rate between all groups. UG and Ualb was significantly increased in ATP6AP2 KO mice on both ND and HFD. ATP6AP2 KO showed greater levels of proximal tubule apoptosis and histologic evidence of proximal tubule injury. In conclusion, our results demonstrate that nephron specific ATP6AP2 KO is associated with glucosuria and albuminuria, most likely secondary to renal proximal tubule injury and/or dysfunction. Urinary loss of nutrients may have contributed to the reduced WT of knockout mice on ND and lack of WT gain in response to HFD. Future investigation should elucidate the mechanisms by which loss of renal ATP6AP2 causes proximal tubule injury and dysfunction.

scholarly journals Renal (Pro)renin Receptor Contributes to High Fat Diet-Induced Obesity

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A55-A55
Author(s):  
Silas Allen Culver ◽  
Helmy M Siragy
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Caloric Intake ◽  
Normal Diet ◽  
High Fat ◽  
Wild Type Littermate ◽  
Littermate Control ◽  
Diet Induced Obesity ◽  
Total Body ◽  
Diet Intake

Abstract Recently we reported that (Pro)renin receptor (PRR) expression increases in the renal nephron during high fat diet intake. This study evaluated the role of renal PRR in the development of obesity. Eight-week old male mice with inducible nephron specific PRR knockout (KO) and wild type littermate (control) were fed either normal diet (ND, 12%kcal fat) or high fat diet (HFD, 45%kcal fat) for 6 months. KO Mice underwent induction of PRR KO with oral doxycycline 2mg/mL in 2% sucrose water for 12 days prior to starting diet. Compared to ND, HFD increased body weight by 40% (p<0.05) in control mice. In contrast, compared to control mice fed HFD, body weight of induced PRR KO on HFD was reduced by 56% (p<0.05). Total body fat increased by 179% (p<0.05) with HFD compared to ND control mice while it did not increase in PRR KO mice fed HFD. Twenty-four-hour caloric intake was not reduced in KO mice compared to controls while there were significant increases in nocturnal VO2 by 31% and respiratory exchange by 10% (p<0.05) in HFD PRR KO mice compared to HFD fed controls. Unexpectedly, urine glucose excretion significantly increased in PRR KO mice on both ND and HFD. Our results demonstrate that nephron specific PRR KO reduced diet induced obesity and adiposity, while increasing energy expenditure. Future investigations are warranted to elucidate the mechanisms by which renal PRR contributes to the development of obesity.

scholarly journals Evaluation of voglibose on body weight in rats

2019 ◽  
Vol 8 (6) ◽  
pp. 1159
Author(s):  
Sarita Mulkalwar ◽  
Tanya Gupta ◽  
Vishwanath Kulkarni ◽  
A. V. Tilak ◽  
B. T. Rane ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
High Fat Diet ◽  
Normal Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Obesity Drugs

Background: As of 2018, 2.1 billion people nearly 30% of the world’s population are either obese or overweight. Worldwide obesity has nearly tripled since 1975. It is an emerging health problem with major adverse effects on health. It is a risk factor for many chronic diseases but is best known for its role in metabolic syndrome, which can lead to type 2 diabetes mellitus as well as cardiovascular diseases. Anti-obesity drugs are available but have many side effects. Voglibose, an antidiabetic drug, is an alpha glucosidase inhibitor which shows promising results in the reduction of body weight with minimal side effects.Methods: Voglibose (7 mg/kg) was administered to rats fed with normal laboratory chows and high fat diet to see its effect on body weight, body mass index, abdominal and thoracic circumference, and lipid profile at the end of 12 weeks.Results: Administration of voglibose significantly reduced food consumption, feed efficiency and increase in body weight induced by high fat diet in rats. Rats fed on normal diet also showed reductions in the same parameters, suggesting its weight lowering effect. Reductions in the anthropometric measurements, hypolipidemic effects and glucose lowering effects were also observed.Conclusions: Voglibose prevented high fat diet-induced obesity and improvement in metabolic profile, which ultimately has systemic effects on body weight in rats. Further studies are needed to see its potential therapeutic use in obese patients with type 2 diabetes mellitus, and related complications.

scholarly journals Antiobesity Effects of an Edible HalophyteNitraria retusaForssk in 3T3-L1 Preadipocyte Differentiation and in C57B6J/L Mice Fed a High Fat Diet-Induced Obesity

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Feten Zar Kalai ◽  
Junkyu Han ◽  
Riadh Ksouri ◽  
Abdelfatteh El Omri ◽  
Chedly Abdelly ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Normal Diet ◽  
Fat Pad ◽  
High Fat ◽  
Regulation Of Expression ◽  
Diet Induced Obesity ◽  
Expression Of Genes ◽  
Nitraria Retusa

Nitraria retusais an edible halophyte, used in Tunisia for several traditional medicine purposes. The present study investigated the antiobesity effects ofNitraria retusaethanol extract (NRE) in 3T3-L1 cells using different doses and in high-fat diet-induced obesity in mice. Male C57B6J/L mice were separately fed a normal diet (ND) or a high-fat diet (HFD) and daily administrated with NRE (50, 100 mg/kg) or one for 2 days with Naringenin (10 mg/kg). NRE administration significantly decreased body weight gain, fat pad weight, serum glucose, and lipid levels in HFD-induced obese mice. To elucidate the mechanism of action of NRE, the expression of genes involved in lipid and carbohydrate metabolism were measured in liver. Results showed that mice treated with NRE demonstrated a significant decrease in cumulative body weight and fat pad weight, a significant lowering in glucose and triglycerides serum levels, and an increase in the HDL-cholesterol serum level. Moreover mRNA expression results showed an enhancement of the expression of genes related to liver metabolism. Our findings suggest that NRE treatment had a protective or controlling effect against a high fat diet-induced obesity in C57B6J/L mice through the regulation of expression of genes involved in lipolysis and lipogenesis and thus the enhancement of the lipid metabolism in liver.

scholarly journals Blimp-1 in adipose resident Tregs controls adipocyte beiging and obesity

2019 ◽  
Author(s):  
Lisa Y. Beppu ◽  
Xiaoyao Qu ◽  
Giovanni J. Marrero ◽  
Allen N. Fooks ◽  
Adolfo B. Frias ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
High Fat Diet ◽  
Caloric Intake ◽  
Transcriptional Regulator ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Visceral Adipose

ABSTRACTCrosstalk between the immune system and adipocytes is critical for maintaining tissue homeostasis and regulating chronic systemic inflammation during diet-induced obesity (DIO). How visceral adipose tissue resident regulatory T cells (aTregs) signal to adipocytes in the visceral adipose tissue (VAT) is not understood. Here we show that Treg-specific ablation of the transcriptional regulator Blimp-1 resulted in increased insulin sensitivity, decreased body weight and increased Ucp-1 in adipocytes in high fat diet (HFD)-fed mice. Mechanistically, we demonstrate that Blimp-1 drives IL-10 production in Tregs, thus suppressing beiging and energy expenditure in adipocytes. Moreover, IL-10 mRNA expression positively correlated with increasing body weight in humans. These findings reveal a surprising relationship between aTregs and adipocytes in promoting insulin resistance during excessive caloric intake, placing Blimp-1-regulated IL-10 expression by aTregs at a critical juncture in the development of obesity and its associated comorbidities in mice and humans.SUMMARYHere we show that ablation of Blimp-1 in adipose tissue resident Tregs (aTregs) leads to decreased IL-10 production, resulting in increased Ucp-1 expression and beiging by adipocytes and protection from diet-induced obesity and insulin resistance.

scholarly journals Anti-Obesity Effects of Morus alba L. and Aronia melanocarpa in a High-Fat Diet-Induced Obese C57BL/6J Mouse Model

Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1914
Author(s):  
Na-Yeon Kim ◽  
Shalom Sara Thomas ◽  
Dae-Il Hwang ◽  
Ji-Hye Lee ◽  
Kyung-Ah Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Normal Diet ◽  
Morus Alba ◽  
High Fat ◽  
Ampk Signaling ◽  
Ppar Γ ◽  
Aronia Melanocarpa ◽  
Diet Induced Obesity ◽  
Fat Volume

The present study investigated the synergic effect of extracts of Morus alba (MA) and Aronia melanocarpa (Michx.) (AR) against high-fat diet induced obesity. Four-week-old male C57BL/6J mice were randomly divided into five groups that were fed for 14 weeks with a normal diet (ND), high-fat diet (HD), HD with M. alba 400 mg/kg body weight (MA), HD with A. melanocarpa 400 mg/kg body weight (AR), or HD with a mixture (1:1, v/v) of M. alba and A. melanocarpa (400 mg/kg) (MA + AR). Treatment with MA, AR, and MA + AR for 14 weeks reduced high fat diet-induced weight gain and improved serum lipid levels, and histological analysis revealed that MA and AR treatment markedly decreased lipid accumulation in the liver and adipocyte size in epididymal fat. Furthermore, micro-CT images showed MA + AR significantly reduced abdominal fat volume. Expression levels of genes involved in lipid anabolism, such as SREBP-1c, PPAR-γ, CEBPα, FAS, and CD36 were decreased by MA + AR treatment whereas PPAR-α, ACOX1, and CPT-1a levels were increased by MA + AR treatment. Protein expression of p-AMPK and p-ACC were increased in the MA + AR group, indicating that MA + AR ameliorated obesity by upregulating AMPK signaling. Together, our findings indicate that MA and AR exert a synergistic effect against diet-induced obesity and are promising agents for managing obesity.

scholarly journals Antiobesity and Hypolipidemic Activity of Moringa oleifera Leaves against High Fat Diet-Induced Obesity in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Souravh Bais ◽  
Guru Sewak Singh ◽  
Ramica Sharma
Keyword(s):  
Body Weight ◽  
Body Temperature ◽  
Total Cholesterol ◽  
High Fat Diet ◽  
Moringa Oleifera ◽  
Chronic Administration ◽  
The Body ◽  
Atherogenic Index ◽  
High Fat ◽  
Diet Induced Obesity

In the present study, the methanolic extract of Moringa oleifera leaves (MEMOL) was evaluated for antiobesity activity in rats. The antiobesity potential of MEMOL was studied against high fat diet-induced obesity (HFD) in rats. In this study, chronic administration of HFD in rats produced hypercholesterolemia (116.2 ± 0.27 mg/dL), which led to an increase in the body weight (225 gr), total cholesterol, triglycerides (263.0 ± 4.69 mg/dL), and attenuation in the levels of HDL (34.51 ± 2.20 mg/dL) as well as changes in body temperature of animals. Treatment of obese rats with MEMOL for 49 days resulted in a significant (P<0.001) change in body weight, total cholesterol, triglycerides, and LDL level along with a significant (P<0.001) increase in body temperature as compared to the HFD-induced obesity. MEMOL treated rats also showed a significant decrease in the level of liver biomarkers, organ weight, and blood glucose level. Further, rats treated with MEMOL (200 mg and 400 mg/kg) show reduced atherogenic index (1.7 ± 0.6 and 0.87 ± 0.76). The results indicate that the rats treated with Moringa oleifera (MO) have significantly attenuated the body weight without any change in the feed intake and also elicited significant thermogenic effect and to act as hypolipidemic and thermogenic property in obesity related disorders.

scholarly journals Influence of gender on OVA-induced airway inflammation in C57/B6J mice on a high-fat diet

2018 ◽  
Vol 16 ◽  
pp. 205873921876094 ◽  
Author(s):  
Gang Yu ◽  
Lili Zhu ◽  
Haiyan Li ◽  
Youyou Shao ◽  
Lei Chong ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Inflammatory Cells ◽  
Normal Weight ◽  
Male Mice ◽  
High Fat ◽  
Low Fat ◽  
Control Male ◽  
Low Fat Diet ◽  
Asthma Group

Overweight/obesity has been suggested as a risk factor for asthma development, and prospective studies have confirmed that high body weight precedes asthma symptoms. However, the nature of the association between overweight/obese status and asthma remains unclear. Animal models of obesity-related asthma are very useful for understanding disease pathophysiology. Although C57/B6J mice are the most widely used animal model for researching obesity-related asthma, gender differences are not always taken into consideration. Therefore, to explore the effect of gender on the development of obesity-related asthma, both female and male C57/B6J mice were used in this study. The mice were fed with a high-fat diet or a low-fat diet as control. Body weight, body length, liver weight, and Lee’s Index were used to evaluate obesity status, and lung histology, lung inflammatory cells infiltration, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were examined for asthma evaluation. We found that the mean body weight of male mice on a high-fat diet gradually increased and was significantly higher than control male mice on a low-fat diet ( P < 0.01), while no significant differences were found between female mice at the end of 12 weeks of feeding. Furthermore, the obese asthma group female and male mice exhibited significantly high inflammatory cells infiltration than normal weight or obese female and male mice ( P < 0.01). However, the obese asthma group presented higher Neu infiltration, Th1 cytokine, and interferon gamma (IFNγ) concentrations in BALF than the asthma group in both the genders ( P < 0.01). In conclusion, both female and male mice are suitable for the obesity-related asthma model, although male mice might be more stable. Besides, obesity-related asthma is not Th2 type asthma.

scholarly journals Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3187
Author(s):  
Eunkuk Park ◽  
Chang-Gun Lee ◽  
Hyoju Jeon ◽  
Hyesoo Jeong ◽  
Subin Yeo ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Insulin Action ◽  
Normal Diet ◽  
Male Mice ◽  
Impaired Glucose Metabolism ◽  
High Fat ◽  
Beneficial Effects ◽  
Cornus Officinalis ◽  
Treatment And Prevention ◽  
Obese Male

Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.

Cholecystokinin knockout mice are resistant to high-fat diet-induced obesity

Appetite ◽  
2011 ◽  
Vol 57 ◽  
pp. S27
Author(s):  
C.M. Lo ◽  
M. Georgievsky ◽  
S.C. Woods ◽  
P. Tso
Keyword(s):  
Knockout Mice ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity
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